Compositions, methods and uses for alpha-1 antitrypsin or derivatives thereof as radioprotectants

Abstract

Embodiments herein report methods and compositions for treating or preventing adverse effects of radiation therapies. In certain embodiments, compositions and methods relate to reducing or inhibiting damage due to acute, periodic or chronic radiation exposure.

1 . A method for ameliorating adverse effects of radiation exposure in a subject comprising, administering to a subject undergoing or scheduled to undergo radiation therapy a therapeutically effective amount of a composition comprising alpha-1 antitrypsin (AAT), a fragment thereof or a mutant thereof wherein the composition modulates the adverse effects of the radiation therapy in the subject. 
     
     
         2 . The method of  claim 1 , wherein the composition comprises naturally occurring AAT (SEQ ID NO:1 or SEQ ID NO:39). 
     
     
         3 . The method of  claim 1 , wherein the composition comprises a composition of one or more carboxyterminal fragments of naturally occurring AAT. 
     
     
         4 . The method of  claim 1 , wherein the subject is undergoing radiation therapy for a condition. 
     
     
         5 . The method of  claim 4 , wherein the condition is cancer. 
     
     
         6 . The method of  claim 1 , wherein the subject has been exposed to radiation as a result of a nuclear accident, nuclear test or nuclear attack. 
     
     
         7 . The method of  claim 1 , wherein the subject has undergone, or is undergoing a diagnostic procedure that comprises exposure to radiation. 
     
     
         8 . The method of  claim 1 , wherein the composition is administered in a therapeutically effective amount to reduce or prevent at least one radiation-induced effect selected from the group consisting of myelosuppression, renal toxicity, weight loss, behavioral changes, pain, nausea, vomiting, diarrhea, constipation, all malnutrition, hair loss, numbness, changes in tastes, loss of appetite, thinned or brittle hair, mouth sores, memory loss, hemorrhage, cardiotoxicity, hepatotoxicity, ototoxicity, and post-chemotherapy cognitive impairment, or a combination thereof. 
     
     
         9 . The method of  claim 8 , wherein the behavioral change is limited mobility. 
     
     
         10 . The method of  claim 1 , wherein the subject is a human subject. 
     
     
         11 . The method of  claim 1 , wherein the composition is administered to the subject in an amount effective to reduce or prevent cellular damage induced by the radiation exposure. 
     
     
         12 . The method of  claim 1 , wherein the therapeutically effective amount of the composition comprises a single intravenous infusion in the subject of AAT at a dose of 1 mg/kg to 150 mg/kg, optionally followed by additional treatments with the composition. 
     
     
         13 . The method of  claim 1 , wherein the therapeutically effective amount of the composition comprises a concentration of AAT of 1 mg/kg to about 150 mg/kg, before, during or after radiation therapy. 
     
     
         14 . The method of  claim 1 , wherein the therapeutically effective amount of the composition comprises a concentration of AAT of 1 mg/kg to about 100 mg/kg administered to the subject every 24 to 48 hours after radiation therapy up to a predetermined time period. 
     
     
         15 . The method of  claim 1 , wherein the administration comprises at least two doses of AAT from about 40 to 80 mg/kg every 24 to 48 hours for a period of from 2 days to 30 days after radiation exposure. 
     
     
         16 . The method of  claim 1 , wherein the radiation exposure comprises an acute or chronic dose of ionizing or non-ionizing radiation. 
     
     
         17 . The method of  claim 16 , wherein the ionizing radiation comprises X-rays. 
     
     
         18 . The method of  claim 16 , wherein the ionizing radiation comprises radionuclides. 
     
     
         19 . The method of  claim 7 , wherein the diagnostic procedure comprises X-rays, a CAT-scan, a mammogram, a radionuclide scan or an interventional radiological procedure under CT or fluoroscopy guidance. 
     
     
         20 . A method for ameliorating adverse effects of exposure to whole body radiation comprising, administering to a subject having been exposed to whole body radiation a therapeutically effective amount of a composition comprising alpha-1 antitrypsin (AAT), a fragment thereof, a recombinant molecule thereof or a mutant thereof wherein the composition modulates the adverse effects of the radiation in the subject. 
     
     
         21 - 27 . (canceled)